Not Miley Cyrus: A small human trial of salvinorin A

Some interesting news came out last week regarding Salvia divinorum, the hallucinogenic mint plant, whose primary active constituent, salvinorin A, is a highly selective kappa opioid receptor agonist that is remarkable as a nonnitrogenous psychoactive compound.

However, my interest had nothing to do with the widely-discussed video at TMZ.com showing actress and singer-songwriter Miley Cyrus doing a bong hit of the plant.

Instead, Dr. Matthew Johnson and colleagues at Johns Hopkins published a report in Drug and Alcohol Dependence on salvinorin A in four, hallucinogen-experienced human subjects that builds upon their investigations of similar compounds in a controlled and supportive clinical setting. Therein, a randomized dose-response study of volatilized salvinorin A revealed that subjects had qualitatively different experiences from other hallucinogens as determined by the use of two detailed measures: the 99-item Hallucinogen Rating Scale designed to show sensitivity to dimethyltryptamine and the 32-item Mysticism Scale used in a study described below to show sensitivity to psilocybin.

Consistent with anecdotal reports, the drug acts quickly with maximal effects at 2-5 minutes and is relatively short-lived with subjective effects returning to baseline by 40 min. However, the subjects did not report any of the dysphoric effects widely popularized in internet videos as noted by Lange et al. (Drug Alcohol Depend 2010; 108:138-140).

In addition, the authors also monitored blood pressure and heart rate and showed that the drug had no effect on either parameter at any of the doses studied. But how these effects and apparent relative acute safety applies outside the clinic is limited by by the sample size, their experience with Salvia, and the precise dosing with inhaled salvinorin A (99.5% by HPLC), relative to the plant material. Moreover, the study was conducted in a living-room like atmosphere with two trained observers and “[a] relaxing instrumental music track (Steven Halpern, “Awakening”, Music for Sound Healing, Inner Peace Music, 1999) was played throughout the session as a continuous loop unlike the chaotic atmosphere apparent in the Miley Cyrus video.

(Incidentally, I am relaxing to Steven Halperin’s “Comfort Zone” while writing this post but with nothing stronger than iced club soda.)

One aim of the legitimate study of hallucinogens and other psychoactive drugs is to identify treatments for schizophrenia and related psychotic disorders. For example, my colleague here at The Haystack blog, Carmen Drahl, wrote this C&EN article two years ago on the an antipsychotic lead compound developed by Lilly to antagonize the effects of the hallucinogen phencyclidine (PCP) at N-methyl-D-aspartate (NMDA) receptors.

In support of this general idea Dr. Roland Griffiths, senior author of the current salvinorin A paper, co-authored an article entitled, Hallucinogens as Medicine, for the December 2010 issue of Scientific American. The article begins with discussion of Griffiths’s study of psilocybin in human volunteers and the remarkable sustained influence of a single experience with the active constituent of the psychoactive mushroom, Psilocybe cubensis. Fourteen months later, more than half of participants ranked the mystical experience of their clinical session with psilocybin as “among the five most personally meaningful and among the five most spiritually significant experiences of their lives,” with two-thirds reporting “increased well-being or life satisfaction.”

The potential for such an experience to influence long-term mental health is certainly worthy of continued study for the simple fact that it seems to have accomplished an endpoint matched only by long-term antidepressant use and psychotherapy. Griffiths and colleagues are perhaps the best-known internationally for these types of controlled studies and are support by funding from the National Institute on Drug Abuse (5R01DA003889).

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